The rodent hepatoma cell lines, Hepa-1 and H-4-II-E-C3, possess high aryl hydrocarbon hydroxylase (AHH) activities. We have previously shown that variants resistant to benzo(a)pyrene (BP) and deficient in AHH can be isolated at low frequency from these lines. In the proposed research we intend to investigate whether mutagens increase the frequency of BP resistant variants of Hepa-1 and to carry out cell-cell hybridization studies with variants of both lines to determine how many complementation groups are involved. Biochemical analyses will be carried out to determine the defects in the variants and if the defect resides in the struture of AHH, we shall investigate which component of this complex enzyme is affected. The variants will be tested for resistance to compounds belonging to other classses of chemical carcinogens and an attempt made to select directly for variants resistant to these chemicals. We shall attempt to isolate carcinogen resistant variants of normal, untransformed rat liver cell lines and investigate the feasibility of a proposed carcinogen screening assay that uses the hepatoma lines.